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Identifier 000419041
Title An in vivo study of the role of Cytochrome P450 and Aldehyde Oxidase on Imidacloprid and Cypermethrin metabolism and related oxidative stress and DNA damage
Alternative Title IN vivo μελέτη του ρόλου του κυτοχρώματος P450 και της aldehyde oxidase στον μεταβολισμό του imidacloprid και του ypermethrin και εκτίμηση του οξειδωτικού στρές και βλαβών του DNA
Author Βαρδαβάς, Αλέξανδρος
Thesis advisor Τσατσάκης, Αριστείδης
Reviewer Carvalho, Felix
Τσατσαράκης, Εμμανουήλ
Θεοδωρόπουλος, Παναγιώτης
Τζαρδή, Μαρία
Νικιτόβιρσ-Τζανακάκη, Ντράγκανα
Τσιαούσης, Ιωάννης
Abstract In this PhD thesis we examined the toxicology aspect of two pesticides, cypermethrin (CY) a synthetic pyrethroid and imidacloprid (IMI) a neonicotinoid and their relevant functions, adverse effects and each pesticide’s more dominant metabolic pathway. Regarding in vivo studies, many pesticides are used in conjunction with Piperonyl Butoxide (PBO) as it is a powerful inhibitor of the oxidative function of Cytochrome P450 (CYP450) and it is also known for its synergistic actions when combined. PBO has become a diagnostic tool for two important aspects of insecticide toxicology which is to determine if an in vivo metabolism of an insecticide is oxidative and to determine if cases of insecticide resistance involve oxidative metabolism by CYP450. The CYP450 mono-oxygenases are a large and functionally diverse family of enzymes that carry out the initial oxidation of a wide variety of lipophilic compounds. These enzymes play a major role in the metabolism of xenobiotics such as drugs, pesticides, carcinogens and other environmental chemicals. It is also known that the metabolites (produced when CYP450 is participated) of CYP450 are responsible for toxicity damage arising from the use of pesticides. Furthermore, neonicotinoids are simultaneously metabolized in vivo by aldehyde oxidase (AOX) from the reduction of the nitro-imino group as well as by CYP450 oxidation reactions. Reduced AOX activity is closely correlated with reduced IMI metabolism to IMI-NNO and IMI-NH, two main metabolic products from the AOX pathway. Finally, metabolites from PBO and AOX reactions are believed to be as potent as the parent compound. This thesis is based on a number of studies each one designed to address a different aspect of the topic. In older studies, CY has not been extensively studied regarding its combination with PBO and neither has PBO been studied based on its inhibition capabilities and its ability to induce toxicity on its own. These comparisons are described in the first publication that focus on the systemic condition of New Zealand male rabbits after long term exposure to CY and PBO based on oxidative stress and telomerase activity test results. In the second publication, a continuation of the first part of the study was conducted to evaluate additionally the liver and kidney inflammation and genotoxicity in New Zealand white male rabbits after long term exposure to CY and PBO. In the last publication, we evaluated the inhibition effectiveness of sodium tungstate dihydrate (ST), an AOX inhibitor, in order to elucidate the relative contribution of CYP 450 and AOX metabolic pathways in IMI metabolism so as to clarify which metabolic pathway is actually more detrimental in New Zealand male rabbits.
Language English
Issue date 2018-12-05
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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